Spatial Transcriptomics for the Analysis of Human Pituitary Development
Spatial Transcriptomics for the Analysis of Human Pituitary Development
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用于分析人垂体发展的空间转录组学
DOI：
10.1210/jendso/bvab048.1129
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发表时间：
2021-05-03
影响因子：
4.1
通讯作者：
Yamamoto T
中科院分区：
文献类型：
--
作者：
Matsumoto R;Kabata M;Suga H;Yamamoto T
垂体由与邻近的下丘脑接触的口腔外胚层发育而成。然而，垂体发育与多种组织协调的确切机制尚未完全了解，尤其是在人类中。从人诱导多能干细胞（hiPSC）诱导垂体细胞的方案已经建立并应用于研究垂体发育和病症。在该方法中，在一个类器官中诱导口腔外胚层和下丘脑，这使得能够再现胚胎发育期间这些组织之间的相互作用。它导致垂体细胞的自我组织。最近，空间转录组技术已经发展并适用于组织相互作用的分析。在这里，我们利用空间转录组学来分析垂体类器官，特别是集中在调节垂体祖细胞分化的机制。空间转录组学显示，类器官由几个细胞群组成，包括下丘脑、口腔外胚层、神经视网膜和皮质神经元细胞。以LHX 3的上调为特征的胎盘祖细胞被包括作为口腔外胚层群体的一部分。对人群的进一步分析确定了人类垂体祖细胞特异性基因，包括许多先天性垂体功能减退症（CPH）的致病基因。最后，使用空间分辨的基因表达数据，我们研究了下丘脑人口与垂体祖细胞接触，并确定下丘脑因子，可能调节祖细胞分化的旁分泌方式。在垂体祖细胞和邻近的下丘脑细胞群中上调的基因是CPH的潜在致病基因候选者。总之，空间转录组学提供了一个新的平台来分析人类垂体发育过程中的组织相互作用网络。
The pituitary develops from oral ectoderm in contact with the adjacent hypothalamus. However, the precise mechanisms underlying pituitary development in concert with plural tissues are not fully understood, especially in human. A protocol to induce pituitary cells from human induced pluripotent stem cells (hiPSCs) has been established and applied to study pituitary development and disorders. In the method, oral ectoderm and hypothalamus are induced in one organoid, which enables recapitulation of the interactions between these tissues during embryonic development. It leads to self-organization of pituitary cells. Recently, spatial transcriptome technology has been developed and is suitable for the analysis of tissue interactions. Here, we utilized spatial transcriptomics to analyze pituitary organoids, especially focusing on the mechanisms regulating pituitary progenitor cell differentiation. Spatial transcriptomics revealed that the organoids consisted of several cell populations including hypothalamus, oral ectoderm, neural retina, and cortex neuron cells. Pituitary progenitor cells, characterized by the upregulation of LHX3, were included as part of the oral ectoderm population. Further analysis of the population identified human pituitary progenitor-specific genes including many causal genes for congenital hypopituitarism (CPH). Finally, using spatially resolved gene expression data, we examined the hypothalamic population that was in contact with pituitary progenitor cells and identified hypothalamic factors that might regulate progenitor cell differentiation in a paracrine manner. The genes upregulated in the pituitary progenitor and neighboring hypothalamus cell populations are potential causal gene candidates for CPH. In conclusion, spatial transcriptomics provides a novel platform to analyze tissue interaction networks during human pituitary development.